The biomedical themes in the Montelione lab include structure-function studies of proteins and complexes involved in cancer biology, neurobiology, and infectious disease. Current focus areas include integral membrane drug transporters of pathogenic bacteria, protein complexes associated with gene integration, DNA damage repair, virus-host interactions, and antivirals targeting SARS CoV2 virus. In addressing these complex systems the lab uses integrative methods combining NMR, crystallography, SAXS, and molecular modeling.

The Montelione lab has made key contributions in computational NMR methods development, including the development of software for automated analysis of protein resonance assignments, automated analysis of 3D structures, and for protein NMR model quality assessment. The lab’s current methods-development focus involves combining contact and distance predictions from bioinformatics together with sparse NMR data to determine the 3D structures of challenging proteins, including membrane proteins.

Montelione served as Director of the NIH Northeast Structural Genomics Consortium (NESG) (2000 – 2016), which developed a successful high-throughput pipeline for protein sample and 3D structure production. The NESG program involved extensive efforts in new technology development for protein sample production, NMR, X-ray crystallography, and structural bioinformatics. More than 1,300 structures were determined by the NESG team. The platform is now being used to enable the structural biology projects funded in the lab, including collaborative efforts in de novo protein design.